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Iron overload resulting from the chronic oral administration of ferric citrate induces parkinsonism phenotypes in middle-aged mice

Iron homeostasis is critical for maintaining normal brain physiological functions, and its mis-regulation can cause neurotoxicity and play a part in the development of many neurodegenerative disorders. The high incidence of iron deficiency makes iron supplementation a trend, and ferric citrate is a...

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Detalles Bibliográficos
Autores principales: Huang, Chao, Ma, Wenjing, Luo, Qihui, Shi, Liangqin, Xia, Yu, Lao, Chengjie, Liu, Wentao, Zou, Yuanfeng, Cheng, Anchun, Shi, Riyi, Chen, Zhengli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874424/
https://www.ncbi.nlm.nih.gov/pubmed/31699955
http://dx.doi.org/10.18632/aging.102433
Descripción
Sumario:Iron homeostasis is critical for maintaining normal brain physiological functions, and its mis-regulation can cause neurotoxicity and play a part in the development of many neurodegenerative disorders. The high incidence of iron deficiency makes iron supplementation a trend, and ferric citrate is a commonly used iron supplement. In this study, we found that the chronic oral administration of ferric citrate (2.5 mg/day and 10 mg/day) for 16 weeks selectively induced iron accumulation in the corpus striatum (CPu), substantia nigra (SN) and hippocampus, which typically caused parkinsonism phenotypes in middle-aged mice. Histopathological analysis showed that apoptosis- and oxidative stress-mediated neurodegeneration and dopaminergic neuronal loss occurred in the brain, and behavioral tests showed that defects in the locomotor and cognitive functions of these mice developed. Our research provides a new perspective for ferric citrate as a food additive or in clinical applications and suggests a new potential approach to develop animal models for Parkinson’s disease (PD).